The goal of the present project is to elucidate the factors which control active vascular smooth muscle (VSM) tone in small resistance vessels during hypertension. Spontaneously hypertensive rats (SHR) in the early (5-7 wks) and established (13-15 wks) stages of hypertension will be compared to age matched normotensive controls (NCR) of the Wistar (WR) and Wistar-Kyoto (WKY) strains. This experimental model has many similarities to human essential hypertension. The cremaster muscle of anesthetized SHR and NCR will be exteriorized and continuously suffused with bicarbonate buffered physiological salt solution (PSS). Indices of microcirculatory functions, VSM tone, and tissue perfusion to be measured include: 1) arteriolar diameters, 2) microvascular pressures, 3) tissue and periarteriolar P02 (02 microelectrodes), 4) intercapillary distances, and 5) microvessel flow velocity. Wall tension and microvessel volume flow will be calculated from measured values. The importance of neural and adrenergic factors in determining VSM tone in SHR and NCR will be evaluated by comparing the above parameters before and after treatment with tetrodotoxin or 6-hydroxydopamine (to eliminate neural influences) and adrenergic blockade (to eliminate effects of circulating or neurally released catecholamines). The degree of active VSM tone in SHR and NCR and its influence upon tissue perfusion will be evaluated by comparing measurements before and after maximal dilation (adenosine or nitroprusside). The importance of the Na+/K+ pump and K+-induced catecholamine release from adrenergic nerves in determining VSM tone in SHR and NCR will be evaluated by measuring arteriolar diameters during alterations in the K+ content of the PSS (in the presence and absence of ouabain, phentolamine, and 6-hydroxy-dopamine). The autoregulatory capacity of small resistance vessels of SHR and NCR will be tested by measuring arteriolar diameters (and other variables) during high and low 02 suffusion and microvascular occlusion (with and without neural and adrenergic blockade). The electrophysiological responses of larger vessels to alterations in 02 availability and to adenosine will be compared by measuring Em in isolated vessels of SHR and NCR. These studies should further clarify the role of neural, adrenergic, and intrinsic VSM properties in determining total peripheral resistance in hypertension.